PROJECT SUMMARY The long term ?goal of this project is to develop a low-cost, user-friendly glucose sensing solution with multi-mode sensing reliability to enable the use of closed-loop insulin delivery safely and reliably in an artificial pancreas. The system has the potential for fast sensor kinetics owing to small size and thin and flexible profile leading to better integration with the surrounding tissue and local vascularization. This can enable automatic closed-loop glucose control without meal announcements and carbohydrate counting. IMS has developed a novel, miniaturized (smaller than half a sesame seed), completely wireless, and extremely low-cost glucose sensor that consists solely of a semiconductor device. This device can sense glucose owing to a novel microelectronics design and an integrated on-chip electrochemical sensor. This device is injected in subcutaneous tissue using a proprietary inserter and wirelessly communicates the glucose data to an external transmitter device which relays it to a smartphone to enable data visualization and cloud-based data handling to provide real-time feedback. With help of Caltech, NIH, and NSF funding, we have e demonstrated sensor functionality in-vitro, in rats, and ?most recently in porcine model for more than 1 month?. Our results indicate the sensor is very accurate (MARD=6.2% for <210 mg/dl which is the most important range), and can work for longer time (3-6 months) after some chemistry improvements i.e. use of catalase to minimize effect of peroxide denaturing of glucose oxidase. Therefore, our ?objective in this proposal is to develop a version of our wireless glucose sensing platform that can measure glucose using ?two different sensing modalities (e.g. differential oxygen measurement, and amperometric peroxide measurement) to ?increase the reliability of the readout. The use of these two modes extend the performance window of the implant by taking advantage of sensitive peroxide detection along with more stable differential oxygen sensing. The sensing platform will be tested in porcine model as it matches well with human skin and metabolism. This research is ?significant as it will enable first factory calibrated, user-insertable and removable, wireless CGM sensor that can work for long time (3-6 months), provide reliability of redundant glucose sensing, and fast response that can all enable safe and accurate closed-loop glucose control in an artificial pancreas. The project ?team ?includes original inventors of the core technology from Caltech (Dr. Nazari, Dr. Rahman, Mr. Sencan), seasoned and respected researcher in Glucose sensor technology (Bill Van Antwerp), experimental surgery and biomaterials expert (Dr. Jonathan Lakey of UC Irvine) and commercialization expert (Mr. Peter Rule from MiniMed, Therasense, and OptiScan). The company is working within IVD Technologies Inc., an ISO certified, FDA registered biotechnology company under a facilities rental agreement.